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In rheumatoid arthritis (RA), fibroblast-like synoviocytes (FLS) present a unique aggressive phenotype and have a passive response to the inflammatory microenvironment, which are critical for the disease's progression. KDM4B, as a histone demethylase, functions as an oncogenic factor in many cancers and is implicated in osteoclastogenesis as well as pro-inflammatory cytokine release in inflammatory diseases. However, the effects of KDM4B on RA FLS have not been reported. To investigate this issue, our study determined the expression of KDM4B in RA FLS using RT-qPCR and western blot. The effects of KDM4B on RA FLS viability, apoptosis, migration, and invasion were detected by MTT, flow cytometry, transwell migration, and invasion assays. Furthermore, the interaction of KDM4B with STAT3 signaling was studied by western blot, MTT, flow cytometry, transwell migration, and invasion assays. The experimental results showed that KDM4B expression was upregulated in RA synovial tissues and FLS as compared to healthy control tissues and normal FLS. Knockdown of KDM4B obviously suppressed RA FLS viability, migration and invasion, and induced apoptosis. In addition, knockdown of KDM4B in RA FLS decreased the expression of p-STAT3 and MMP-9 but increased cleaved caspase-3 expression compared with the control group. Moreover, KDM4B overexpression could promote cell growth, migration and invasion, and suppress apoptosis in RA FLS by activating STAT3 signaling. Therefore, these findings provide new insight for understanding the pathogenesis of RA and indicate that KDM4B may have a potential to be an effective therapeutic target for RA.In this Review (Part I), we investigate the scientific evidence that multiple sclerosis (MS) is caused by the death of oligodendrocytes, the cells that synthesize myelin, due to a lack of biochemical and nutritional factors involved in mitochondrial energy production in these cells. In MS, damage to the myelin sheaths surrounding nerve axons causes disruption of signal transmission from the brain to peripheral organs, which may lead to disability. Cryptotanshinone manufacturer However, the extent of disability is not deterred by the use of MS medication, which is based on the autoimmune hypothesis of MS. Rather, disability is associated with the loss of brain volume, which is related to the loss of grey and white matter. A pathology-supported genetic testing (PSGT) method, developed for personalized assessment and treatment to prevent brain volume loss and disability progression in MS is discussed. This involves identification of MS-related pathogenic pathways underpinned by genetic variation and lifestyle risk factors that may converge into biochemical abnormalities associated with adverse expanded disability status scale (EDSS) outcomes and magnetic resonance imaging (MRI) findings during patient follow-up. A Metabolic Model is presented which hypothesizes that disability may be prevented or reversed when oligodendrocytes are protected by nutritional reserve. Evidence for the validity of the Metabolic Model may be evaluated in consecutive test cases following the PSGT method. In Part II of this Review, two cases are presented that describe the PSGT procedures and the clinical outcomes of these individuals diagnosed with MS.This study applies positive psychology to improve EFL learners' listening comprehension ability. To this aim, two groups of EFL learners (N = 45) participated in the study. The learners in the experimental group received the positive psychology intervention based on four components of positive psychology including hope, gratitude, emotion regulation, and empathy and those in the control group received the usual listening comprehension activities. The results including listening comprehension scores along with the analysis of the semi-structured interviews and class observations showed the effectiveness of the intervention, highlighting an increase in the students' listening comprehension scores. It was found that the experimental group experienced a range of positive and negative emotions, with positive emotions more than twice as frequent as negative emotions. The findings also showed that the intervention informed the instructor regarding specific areas where the learners encountered difficulty and in so doing, it allowed for applying appropriate strategies to help them overcome such problems. Finally, the theoretical and pedagogical implications of integrating positive emotions in foreign language teaching are discussed.
The aim of this review article is to give an overview over recent experimental neurobiological research on dissociation in borderline personality disorder (BPD), in order to inform clinicians and to stimulate further research. First, we introduce basic definitions and models that conceptualize dissociation from a transdiagnostic perspective. Then, we discuss recent findings in BPD.
Stress-related dissociation is a key symptom of BPD, closely linked to other core domains of the disorder (emotion dysregulation, identity disturbances, and interpersonal disturbances). The understanding of neurobiological correlates of dissociation across different psychiatric disorders (e.g., dissociative disorders, post-traumatic stress disorder) is steadily increasing. At the same time, studies explicitly focusing on dissociation in BPD are still scarce. There is evidence for adverse effects of dissociation on affective-cognitive functioning (e.g., interference inhibition), body perception, and psychotherapeutic treatment r disorder) is steadily increasing. At the same time, studies explicitly focusing on dissociation in BPD are still scarce. There is evidence for adverse effects of dissociation on affective-cognitive functioning (e.g., interference inhibition), body perception, and psychotherapeutic treatment response in BPD. On the neural level, increased activity in frontal regions (e.g., inferior frontal gyrus) and temporal areas (e.g., inferior and superior temporal gyrus) during symptom provocation tasks and during resting state was observed, although findings are still diverse and need to be replicated. Conceptual differences and methodological differences in study designs and sample characteristics (e.g., comorbidities, trauma history) hinder a straightforward interpretation and comparison of studies. Given the potentially detrimental impact of dissociation in BPD, more research on the topic is strongly needed to deepen the understanding of this complex clinical condition.
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